Phenyl isocyanate → (trans)-1-(6-Cyano-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-phenylurea

HRID 129177Notes

Reaction equation

HRID 129177 reaction equation
[NH2:1][C@@H:2]1[C:7]2[CH:8]=[C:9]([C:12]#[N:13])[CH:10]=[CH:11][C:6]=2[O:5][C:4]([CH3:15])([CH3:14])[C@H:3]1[OH:16].[C:17]1([N:23]=[C:24]=[O:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(O)C>[C:12]([C:9]1[CH:10]=[CH:11][C:6]2[O:5][C:4]([CH3:14])([CH3:15])[C@@H:3]([OH:16])[C@H:2]([NH:1][C:24]([NH:23][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:25])[C:7]=2[CH:8]=1)#[N:13]

Participants

4

Reactant 2

HCID 7672Phenyl isocyanateHCID 10943936(3S,4R)-4-amino-3-hydroxy-2,2-dimethyl-chroman-6-carbonitrile

Product 1

HCID 9905823(trans)-1-(6-Cyano-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-phenylureaYield 63%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A suspension of (trans)-4-amino-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (prepared according to Evans et al., J. Med. Chem., 1983, 26, p. 1582 and J. Med. Chem., 1986, 29, p. 2194) (1.0 g, 4.6 mmol) in ethanol (4 ml) under argon was treated with phenylisocyanate (0.55 g, 4.6 mmol) and the reaction was heated at reflux temperature for 4 hours. The product precipitate out of the reaction. The reaction was then concentrated in vacuo and the residue was triturated with isopropylether to give the title compound as a colorless solid (0.9 g, 63%), m.p. 240°-241° C.: 1H NMR (CDCl3 /DMSO) δ8.3 (s, 1H), 7.7 (s, 1H), 7.4 (d, J=8.0 Hz, 3H), 7.26 (t, J=8.0 Hz, 2H), 7.0 (t, J=9.0 & 7.0 Hz, 1H), 6.86 (d, J=9.0 Hz, 1H), 6.4 (d, J=8.0 Hz, 1H), 5.3 (d, J=5.0 Hz, 1H), 4.9 (t, J=9.0 & 8.0 Hz, 1H), 3.6 (dd, J=4.0 & 6.0 Hz, 1H), 1.5 (s, 3H), 1.3 (s, 3H); 13C NMR (CDCl3 /DMSO) 157.0, 156.5, 139.1, 132.2, 132.1, 128.4, 123.9, 121.8, 118.2, 117.8, 80.0, 74.3, 49.9, 26.1, 18.4; IR (KBr) 1132, 1267, 1491, 1550, 1612, 1645, 2226, 2932, 2978, 3433 cm-1.

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux temperature for 4 hours
  3. customThe product precipitate out of the reaction
  4. concentrationThe reaction was then concentrated in vacuo
  5. customthe residue was triturated with isopropylether

Sources & evidence

ORD record
ord-258573784296464fb4a98d0d2c04d23d
Source dataset
uspto-grants-1995_11
Patent number
US05466817

Reaction notes

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